Oxidant stress and adult respiratory distress syndrome.
Several experimental and theoretical lines of evidence implicate oxidant mechanisms in the diffuse lung injury which leads to the clinical syndrome called the adult respiratory distress syndrome (ARDS). The fact that the injury is characterized by diffuse lung inflammation and that neutrophils can injure lung cells by producing reactive oxygen species provide all of the events necessary for extracellular oxidant stress as an important mechanism of injury. In experimental models and in the clinical syndrome, biochemical evidence of oxidant injury can be measured in the form of lipid peroxidation products. In some models, antioxidants, even antioxidant enzymes which do not access cell interiors, can protect the lungs from injury. There is also evidence that reactive oxygen species generated within lung cells may provide an additional oxidant mechanism of injury. Gram negative bacterial endotoxin can directly injure lung endothelial cells in culture. This injury is unaffected by superoxide dismutase or catalase (antioxidant enzymes which do not enter cells), but is prevented by several antioxidants which penetrate cells (including dimethyl sulphoxide, dimethyl thiourea and allopurinol). The fact that allopurinol can inhibit direct lung cell injury by endotoxin suggests that xanthine oxidase may be a source of oxidant generation in lung endothelial cells. Current data suggest a two stage oxidant process of lung cell injury where there is both direct injury of the cell by intracellular generation of toxic oxidants and triggering of the inflammatory response. Activated inflammatory cells adherent to lung cells then enhance the injury by the generation and release of extracellular oxidants.
Brigham
K L
KL
Dept of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
D000111:Acetylcysteine / Q000627:therapeutic use; D000818:Animals; D005609:Free Radicals; D006801:Humans; D008168:Lung / Q000473:pathology*; D010100:Oxygen / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology
D005609:Free Radicals; D010100:Oxygen; D000111:Acetylcysteine